Pyrimidine compound and anti-rotavirus composition

Abstract

A pyrimidine compound of the formula [I]wherein R1 is H, C1-C4 lower alkyl, halogen atom, -OH, C1-C4 lower alkoxy, C1-C6 hydroxy(lower)alkoxy or -NH2; R2 is H, -NH2 or -NHCOCH3; R3 is -NR5(CH2)i-CH2OH; R4 is H, halogen atom, -NH2, -CN, -CHO, -CH2OH, -COOH, -CH2NH2, -CONH2 or -CH=N-A wherein A is -OH, C1-C4 lower alkyl or C1-C4 lower alkoxy; R5 is H or C1-C4 lower alkyl; and i is an integer of 1 to 4, and an anti-rotavirus agent comprising, as an active ingredient, a compound of the formula [I] wherein R3 is a group selected from the following: The novel pyrimidine compound of the present invention and related derivatives thereof have superior anti-rotavirus action and are useful for the prophylaxis and treatment of rotaviral diseases.

What is claimed is: 
     
       1. A pyrimidine compound of the formula (I) ##STR140## wherein R1 is H, C 1  -C 4  alkyl, halogen atom, --OH, C 1  -C 4  alkoxy, C 1  -C 6  hydroxyalkoxy or --NH 2  ; R2 is --NH 2  or --NHCOCH 3  ;   R3 is --NR5(CH 2 ) i  --CH 2  OH;   R4 is H, halogen atom, --NH 2 , --CN, --CHO, --CH 2  OH, --COOH, --CH 2  NH 2 , --CONH 2  or --CH═N--A, wherein A is --OH, C 1  -C 4  alkyl or C 1  -C 4  alkoxy;   R5 is H; and   i is an integer of 1 to 4,   or a pharmacologically acceptable salt thereof.   
     
     
       2. A pharmaceutical composition comprising a pyrimidine compound of claim 1 or a pharmacologically acceptable salt thereof and a pharmacologically acceptable carrier. 
     
     
       3. A method for the prophylaxis and treatment of diseases in a host caused by infection by rotaviruses, which comprises administering to a host an effective amount of a pyrimidine compound of claim 1 or a pharmacologically acceptable salt thereof. 
     
     
       4. A method for the prophylaxis and treatment of diseases in a host caused by infection by rotaviruses, which comprises administering to a host an effective amount of a pyrimidine compound of the formula (I) ##STR141## wherein R1 is H, C 1  -C 4  alkyl, halogen atom, --OH, C 1  -C 4  alkoxy, C 1  -C 6  hydroxyalkoxy or --NH 2  ; R2 is H, --NH 2  or --NHCOCH 3  ;   R3 is --NR5(CH 2 ) i  --CH 2  OH;   R4 is H, halogen atom, --NH 2 , --CN, --CHO, --CH 2  OH, --COOH, --CH 2  NH 2 , --CONH 2  or --CH═N--A wherein A is --OH, C 1  -C 4  alkyl or C 1  -C 4  alkoxy;   R5 is H or C 1  -C 4  lower alkyl; and   i is an integer of 1 to 4,   or a pharmacologically acceptable salt thereof.   
     
     
       5. A method for the prophylaxis and treatment of diseases in a host caused by infection by rotaviruses, which comprises administering to a host an effective amount of pyrimidine compound of the formula (I') ##STR142## wherein R1 is H, C 1  -C 4  alkyl, halogen atom, --OH, C 1  -C 4  alkoxy, C 1  -C 6  hydroxyalkoxy or --NH 2  ; R2 is H, --NH 2  or --NHCOCH 3  ;   R3' is a group selected from the group consisting of the following (a) to (e): ##STR143## wherein R5 is H or C 1  -C 4  lower alkyl,   R6 and R7 are the same or different and each is C 1  -C 4  lower alkyl,   R8 is H, --OH, C 1  -C 4  hydroxyalkyl or --CH 2  OC(O)CH 3 ,   R9 is H, --OH, C 1  -C 4  alkyl, C 1  -C 4  hydroxyalkyl, C 1  -C 4  lower alkoxy, vinyl, --O(CH 2 ) k  --R where R is aromatic ring optionally having, on its ring, a substituent selected from the group consisting of C 1  -C 4  alkyl, halogen atom and C 1  -C 4  alkoxy, and k is an integer of 0 to 4, or --(CH 2 ) j  --R', where R' is benzoyloxy or aromatic ring optionally having, on its ring, a substituent selected from C 1  -C 4  lower alkyl, halogen atom, and C 1  -C 4  alkoxy, and j is an integer of 0 to 6,   R10 is H, --OH or C 1  -C 4  alkoxy,   R9 and R10 may form a methylene group (═CH 2 ) or a carbonyl (C═O) together with the carbon atom to which they are bonded,   in the formulas (c) and (e), cycloalkyl ring may have a double bond at an optional position in the ring,   i is an integer of 1 to 4,   n is an integer of 0 to 4, and   m is an integer of 0 to 4; and   R4 is H, halogen atom, --NH 2 , --CN, --CHO, --CH 2  OH, --COOH, --CH 2  NH 2 , --CONH 2  or --CH═N--A where A is --OH, C 1  -C 4  alkyl or C 1  -C 4  alkoxy,   exclusive of when n is 0 and R8 is H;   or a pharmacologically acceptable salt thereof.   
     
     
       6. The method of claim 5, wherein j is an integer of 0 to 4.